Technologies for encapsulating a useful substance in a liposome, which is a vesicle formed of an artificial bilayer, are actively studied in the fields of pharmaceutical drugs, cosmetics, foods, dyes and the like.
Widely used lipids for forming a layer of a liposome include, for example, a combined lipid of a layer-forming lipid such as diacylphosphatidylcholine, cholesterol or the like and a negatively charged phospholipid such as diacylphosphatidylglycerol, diacylphosphatidylinositol, diacylphosphatidylserine or the like.
It is relatively easy to produce a liposome formulation which can suppress the in vivo decomposition or control the in vivo kinetics of a drug when administered to a living organism, but it is quite difficult to construct a formulation having properties which can also improve the intracellular migration capability of a drug. The reason for this is that a liposome formulation is intended to improve the drug concentration in the vicinity of a target tissue or cell by controlling the in vivo kinetics of the drug encapsulated therein, and the ease of migration into the cell depends on the permeability of a particular drug through the bilayer of the liposome and the cell membrane. When the target is a phagocyte such as a macrophage, a monocyte or the like, however, the intracellular migration capability of the drug may occasionally be improved because the phagocyte easily takes in a microparticle such as a liposome or the like.
Recently, it has been studied to introduce a gene into a cell by forming a complex of the gene and an independent cationic lipid or a liposome containing the cationic lipid. However, use of such a carrier having an intracellular migration capability has problems that (1) it is difficult to synthesize a cationic lipid, (2) the resultant formulation is expensive, and (3) the carrier has a high level of cytotoxicity.
As a cationic lipid, an amino acid type lipid containing dialkylaspartic acid linked to lysine has been reported (Hong Sung Kim et al., Gene-Transferring Efficiencies of Novel Diamino Cationic Lipids with Varied Hydrocarbon Chans, Bioconjugate Chem. 2004, 15, 1095). However, this lipid has problems of being unlikely to assume a vesicle structure easily and being unstable in a dispersed state.
In view of the above-described situations, it is desired to develop a cationic lipid which (1) is easy to be synthesized, (2) can be provided at low cost, and (3) is highly biocompatible, i.e., is low in toxicity.